Polybutylbenzylphenols and benzyl-3,4-methylenedioxybenzenes in insect population control

ABSTRACT

Certain polybutylbenzylphenols and benzyl-3,4-methylenedioxybenzenes are useful for insect control especially as insect chemosterilants and oviposition inhibitors. The benzyl-3,4-methylenedioxybenzenes also find utility as growth inhibitors for mosquito larvae.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to and has among its objects the provision ofnovel organic compounds and the use thereof in insect control,particularly as anti-procreants. Further objects of the invention willbe evident from the following description wherein parts and percentagesare by weight unless otherwise specified. The symbol φ is used herein torepresent the ##STR1##

2. Description of the Prior Art

Currently, there are various means for controlling insect populations.For example, one may apply an insecticide to insects or to theirhabitat. This method of control, however, has the disadvantage that theinsecticide may cause harm to humans, animals, and useful insects (bees,for instance). Biological control of insects may be attained byemploying compounds which serve as anti-procreants, i.e.,chemosterilants or oviposition inhibitors. In the first type ofbiological control, a chemical (called a chemosterilant) is administeredto the insects, which then become sexually sterile. The sexuallysterilized insects mate with fertile insects, but the eggs laid do notyield any progeny. The result is a decrease in population of theinsects. Another method of biological control involves administering achemical (oviposition inhibitor) to the insects, with the result thatthe female species do not posit (lay) any eggs. Consequently, noprogency are produced and a decrease in insect population is thusattained. Although the above means of biological control encompass twodistinct ideas, the chemical compounds which produce the above effectsmay be termed generally as anti-procreants, that is, compounds which acteither as chemosterilants and/or oviposition inhibitors and preventprocreation of the species.

The biological method of insect control offers many advantages over theusual method of applying an insecticide to insects or their habitat. Forexample, it avoids harm to humans, animals, and useful insects.

In controlling insects by sterilization or oviposition inhibition, asuitable compound is administered to a group of insects and these arethen released in a locus where insects of the same species are present.As noted above, the treated insects mate with fertile ones but withoutproducing progeny so that the overall population is decreased.

Insect anti-procreants are known and described in U.S. Pat. Nos.3,959,489 ('489), 4,049,722 ('722), and 3,968,234 ('234). In '489 and'722 sexual sterility and oviposition in flies were inhibited by feedingthe flies sufficient amounts of the following compounds: ##STR2##wherein n is 2 or 3.

Sexual sterility, but not oviposition inhibition, was obtained in '234by employing compounds of the structure ##STR3## wherein Alk is an alkylradical containing 1 to 4 carbon atoms.

Another means for controlling insect populations involves the use ofcompounds which inhibit the growth of the insect larvae. Such compoundsare often referred to in the art as juvenile hormone mimics. Theseagents do not kill the larvae, but rather prevent the growth thereofbeyond the larval or pupal stage. Consequently, the number of adults issubstantially reduced. The juvenile hormone mimics actually causeseveral different situations, all of which result in controlling insectpopulation. First of all, most of the treated larvae do not reachadulthood. Thus, the larvae survive for a period of time (possibly anentire growing season) as either larvae or pupae, and then die. Duringthat period the larvae are, of course, very susceptible to predation andinjurious climatic conditions. Furthermore, they are themselvesincapable of reproduction, thus reducing the insect population for thenext growing season. Secondly, some of the treated larvae may develop tovarious stages of adulthood. For example, the adult insect may onlypartially eclose, i.e., emerge from the larval or pupal shell. On theother hand, full eclosion may occur but the adult insect is eithermalformed or dead. In either case, the population of adult insects issubstantially reduced.

The growth-inhibiting compounds have many advantages over insecticidesand the like. First, the growth-inhibitors do not yield unwantedecological side effects. Secondly, since the growth inhibitors act asjuvenile hormone mimics, the insects do not develop a tolerance to thecompounds. Thus, the compounds will not eventually become ineffective.Third, the growth-inhibiting compounds are not harmful to beneficialinsects or mammals because they are quite specific for a particular kindof insect.

Larval growth-inhibiting compounds have been disclosed. For example, inChemical Abstracts, Volume 80, No. 768 h (1974), and Mosquito News,Volume 31, No. 4, pp. 513-516 (1971), certain polybutylbenzyl phenolsare offered as insecticides to control mosquitos. Generally, thesecompounds have the structure ##STR4## wherein R is independentlyhydrogen or methyl.

Finally, the following compound was described as a mosquito larvicidalagent in Chemical Abstracts, Volume 82, 125071 y (1975) and in GermanOffen. 2,425,713: ##STR5##

It should be noted that sexual sterility and oviposition inhibition, onthe one hand, and larvicidal or juvenile hormone activity, on the other,although related generally because they are forms of insect populationcontrol, are different and unrelated concepts. In the former, insectsexposed to the anti-procreant agents exhibit one or both of thefollowing results: First, females may not posit any eggs. Second, eventhough eggs are posited, they do not hatch or otherwise further developbecause the anti-procreant compound has induced sexual sterility ineither the adult male or adult female or both. In any case, procreationis prevented.

Juvenile hormones are essential for growth and development of youndlarvae. The last instar larvae are equipped with internal physiologicalmechanisms which interrupt the secretion of these juvenile hormones. Theresult is that larval growth and development are replaced by pupal andadult growth--a process generally known as metamorphosis. Themetamorphic process can be thwarted by supplying the larvae withjuvenile hormone or a juvenile hormone analogue before a certaincritical period is reached. If this is done, partial or completeinhibition of metamorphosis is realized and adults either do not form orare misformed.

SUMMARY OF THE INVENTION

I have found that certain polybutylbenzylphenols andbenzyl-3,4-methylenedioxybenzenes are useful in controlling insectpopulation especially as insect anti-procreants. In addition, thebenzyl-3,4-methylenedioxybenzenes serve as juvenile hormone mimics formosquito larvae. The instant compounds have an activity equal to orgreater than known compounds. Furthermore, by compounds apparently lacktoxic and mutagenic properties possessed by many known insectanti-procreants and juvenile hormone mimics.

The compounds of the invention may be categorized as follows:

Group I. Polybutyl-2-benzyl phenols of the structure ##STR6## wherein nis an integer from 1 to 3

R is hydrogen or lower alkyl containing from 1 to 6 carbon atoms

R₁ is hydrogen, lower alkyl containing from 1 to 6 carbon atoms, orlower alkoxy containing from 1 to 6 carbon atoms.

Group II. Polybutyl-4-benzyl phenols of the structure ##STR7## wherein Ris hydrogen or lower alkyl containing from 1 to 6 carbon atoms.

Group III. Benzyl-3,4-methylenedioxybenzenes of the structure ##STR8##wherein R₂ is hydrogen, lower alkyl containing from 1 to 6 carbon atoms,lower alkoxy containing from 1 to 6 carbon atoms, or lower alkenylcontaining 2 to 6 carbon atoms,

R₃ is hydrogen or lower alkyl containing from 1 to 6 carbon atoms,

R₄, R₅ and R₆ are independently hydrogen, lower alkyl containing from 1to 6 carbon atoms, and lower alkoxy containing from 1 to 6 carbon atomsand

wherein, if R₂ is hydrogen, then R₅ and R₆ must be independently loweralkyl containing from 1 to 6 carbon atoms or lower alkoxy containingfrom 1 to 6 carbon atoms and

wherein, if R₄, R₅, and R₆ are hydrogen and R₃ is methyl, then R₂ mustbe alkoxy containing 2-5 carbon atoms.

Group IV. 3,4-Methylenedioxybenzyl-3,4-methylenedioxybenzenes of thestructure ##STR9## wherein R₇ is lower alkyl containing 1 to 6 carbonatoms, lower alkoxy containing 2 to 6 carbon atoms, or lower alkenylcontaining 2 to 6 carbon atoms, and

R₈ is hydrogen or lower alkyl containing from 1 to 6 carbon atoms.

The compounds of Groups III and IV are novel; the compounds of Group Iwherein R₁ is other than hydrogen are also novel.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In one phase of the invention, insects are rendered either sexuallysterile or, in the case of female insects, incapable of oviposition byadministering to them any of the compounds heretofore described. Theso-treated insects are then ready for release in insect breeding areasfor mating with fertile insects of the same species. The administrationof the compounds may be carried out by feeding the insects on aconventional insect food to which is added any of the aforesaidcompounds in a concentration which is sufficient to induce either sexualsterility or oviposition inhibition in the insects, but is insufficientto kill them. The concentration required to achieve sterility oroviposition inhibition will vary depending on such factors as the kindof insect and the activity of the selected anti-procreant. It should benoted that the compounds of the invention are capable of acting aseither a chemosterilant or an oviposition inhibitor depending on theparticular concentration administered to the insects. As achemosterilant the compounds are employed generally in a concentrationof about 250 to 10,000 ppm; whereas about 500 to 10,000 ppm arenecessary for oviposition inhibition. In any particular case theappropriate amount to use can readily be determined by pilot testswell-known to entomologists. The anti-procreants of the invention can beadministered to captive insects in cages or other suitable containers.Alternatively, the anti-procreants may be administered to wild insects,for example, by making available to them feeding stations provided foringestion by the insects with food admixed with any of theanti-procreants in either a sterilizing or an oviposition inhibitingproportion. Other methods of administering the instant compounds toinsects will be evident to those skilled in the art and are includedwithin the scope of my invention.

I have also discovered that the compounds of Groups III and IV arehighly effective growth inhibitors for mosquito larvae. In accordancewith this embodiment of my invention any one of these compounds isapplied in a growth-inhibiting amount to the habitat or breeding placeof the mosquito larvae, e.g., added to the water wherein the larvae arepresent. As a result, the growth of the mosquito larvae beyond thelarval or pupal stage is inhibited so that few, if any, adult mosquitosare formed. The concentration of the compound required to achieve growthinhibition will vary depending on the activity of the selected compound.In any particular case the appropriate amount to use can readily bedetermined by pilot tests well-known to entomologists. In many casesgood results have been attained where the compounds are applied in aconcentration of about 0.01 to 1 ppm in bodies of water where themosquito larvae exist. The growth inhibitors of the invention areeffective only on mosquito larvae; they have no effect on adultmosquitoes and consequently must be administered to the larvae to attainthe desired result of growth inhibition.

Because the compounds of the invention are effective in very minorconcentrations, it is preferred that they be dissolved or suspended in acarrier prior to application to the breeding centers. The solution orsuspension increases the bulk, and thus makes it easy to administersmall amounts of the compounds to the mosquito breeding area. Solventsappropriate for this purpose should be volatile ones, such as acetone,ethyl ether, ethanol, benzene, xylene, petroleum naphtha, and the like.

It is within the compass of the invention to use a single compound asherein described or mixtures of two or more of these compounds.

Typical examples of compounds which may be used in the method of theinvention are the following:

Group I: 4,6-di-t-butyl-2-benzyl phenol;4,6-di-t-butyl-2-(α-alkylbenzyl) phenols, wherein the α-alkyl group ismethyl, ethyl, propyl, butyl, pentyl, and hexyl, respectively;4,6-di-t-butyl-2-(4-alkoxybenzyl) phenols, wherein the 4-alkoxy group ismethoxy, ethoxy, propoxy, butoxy, pentoxy, and hexoxy, respectively;4,6-di-t-butyl-2-(4-alkylbenzyl) phenols wherein the 4-alkyl group ismethyl, ethyl, propyl, butyl, pentyl, hexyl, respectively;4,6-di-t-butyl-2-(4-alkoxy-α-alkylbenzyl) phenols, wherein the 4-alkoxyand the α-alkyl groups are those listed above; and4,6-di-t-butyl-2-(4-alkyl-α-alkylbenzyl) phenols wherein the 4-alkyl andthe α-alkyl groups are those listed above.

Group II: 2,6-di-t-butyl-4-(α-alkylbenzyl) phenols wherein the α-alkylgroup is methyl, ethyl, propyl, butyl, pentyl, and hexyl.

Group III: (4-alkoxybenzyl)-3,4-methylenedioxy-6-alkoxybenzenes whereinthe 6-alkoxy group and the 4-alkoxy group are independently methoxy,ethoxy, propoxy, butoxy, pentoxy, and hexoxy, isopropoxy, t-butoxy,iso-butoxy, t-amyloxy, isopentoxy, isohexoxy;(α-methyl-4-alkoxybenzyl)-3,4-methylene-dioxy-6-alkoxybenzenes whereinthe 6-alkoxy group and the 4-alkoxy group are those listed above, andthe α-alkyl group is methyl, ethyl, propyl, butyl, pentyl, or hexyl;(α-methylbenzyl)-3,4-methylenedioxy-6-alkoxybenzenes wherein theα-methyl group is from the above-listed alkyl groups and the 6-alkoxygroup is ethoxy, propoxy, butoxy, or pentoxy;(4-alkoxybenzyl)-3,4-methylenedioxy-6-alkenylbenzenes wherein the6-alkenyl group is ethenyl, propenyl, butenyl, pentenyl, or hexenyl andthe 4-alkoxy group is one of the aforementioned;(4-alkoxybenzyl)-3,4-methylenedioxy-6-alkylbenzenes wherein the 6-alkylgroup is methyl, ethyl, propyl, butyl, pentyl, or hexyl;(3-alkyl-4-alkoxybenzyl)-3,4-methylenedioxybenzenes wherein the 4-alkoxygroup is selected from the group listed above and the 3-alkyl group ismethyl, ethyl, propyl, butyl, pentyl, or hexyl,(3,5-dialkyl-4-alkoxybenzyl)-3,4-methylenedioxybenzenes wherein the4-alkoxy group is one of those listed above and the 3,5-dialkyl groupsare independently methyl, ethyl, propyl, butyl, pentyl, or hexyl;(2,4-dialkoxybenzyl)-3,4-methylenedioxybenzenes wherein the 2,4-dialkoxygroups are independently methoxy, ethoxy, propoxy, butoxy, pentoxy, orhexoxy; (2-methyl-4-alkoxy-5-isopropylbenzyl)-3,4-methylenedioxybenzeneswherein the 4-alkoxy group is methoxy or n-propoxy.

Group IV: (6-Alkoxy-3,4-methylenedioxybenzyl)-3,4-methylenedioxybenzenes wherein the 6-alkoxy group is methoxy, ethoxy, propoxy,butoxy, pentoxy, or hexoxy;(α-alkyl-6-alkoxy-3,4-methylenedioxybenzyl)-3,4-methylenedioxy-benzeneswherein the α-alkyl group is methyl, ethyl, propyl, butyl, pentyl, orhexyl, and the 6-alkoxy group is selected from the aforementioned group.

The compounds of Groups I and II, except where either R or R₁ ishydrogen but not both, may be prepared by refluxing a mixture of theappropriate polybutyl phenol with the appropriate alcohol in an aqueousacid medium. For example, 4,6-di-t-butyl-2-benzylphenols can be preparedby reacting 2,4-di-t-butylphenol with the appropriate alcohol underreflux in the presence of aqueous formic acid. This synthesis isillustrated by the following formulas ##STR10## wherein R and R₁ aredefined as described above. To prepare 2,6-di-butyl-4-benzyl phenols oneproceeds as follows: ##STR11## wherein R is defined as described above.

The remaining compounds of Groups I and II can be synthesized byappropriate condensation reactions such as the Friedel-Crafts reactionand the like.

Similarly, most of the compounds of Groups III and IV can be prepared bycondensation of 3,4-methylenedioxyphenol with the appropriate alcohol inan aqueous acidic medium and then formation of an alkyl ether.Schematically, the reaction may be represented as follows: ##STR12##wherein R₃ to R₆ are defined as above.

Some of the Group III compounds are prepared by reaction of theappropriate lower alkenyl-substituted 3,4-methylenedioxybenzene and theappropriate alcohol. ##STR13## wherein the lower alkenyl group containsfrom 2 to 6 carbon atoms and R₃ to R₆ are defined as describedhereinabove.

Similarly compounds of Group IV wherein R₇ is lower alkyl or alkenyl canbe prepared from a lower alkyl- or alkenyl-substituted3,4-methylenedioxybenzene and an appropriate alcohol. ##STR14##

To prepare the compounds of Group IV wherein R₇ is lower alkoxy3,4-methylenedioxyphenol is condensed with a substitutedα-hydroxymethyl-3,4-methylenedioxyphenol followed by alkylation to formthe alkyl ether. ##STR15##

Another aspect of my invention concerns a novel synthesis of the Group Icompounds. I have found that these compounds can be prepared by simplyadmixing the appropriate polybutylphenol with the appropriate alcoholand heating the mixture for a period of about 0.5 to 2.0 hours. Thetemperature of the reaction is about 170° to 220° C. Generally, about0.5 to 1.0 parts of alcohol are used per part of polybutylphenol. Theresulting product is recovered from the reaction mixture by conventionaltechniques including fractional distillation and crystallization fromsolvents.

The above-described synthetic procedure avoids the cumbersome stepsencountered when an aqueous acidic medium is employed. Furthermore, theyields of the final product in both synthetic approaches are comparable.

The following schematic representation illustrates my novel syntheticapproach by way of example: ##STR16## wherein R and R₁ are defined asdescribed above.

It should be noted that my novel synthesis for the preparation of thecompounds of Group I cannot be employed to prepare the compounds ofGroup II. The compounds of Groups III and IV can be synthesized asdescribed above if a small amount, 0.05 to 0.5%, of a weak acid such ascitric acid, oxalic acid, hypophosphorous acid, and so forth is added tothe reaction mixture.

The activity of the compounds of Groups I to IV is unexpected and notshared by closely-related compounds. For example, the followingcompounds are ineffective in my method: 2-benzyl-4-t-butylphenol,2-(α-methylbenzyl)-4-t-butylphenol,4-(α,α-dimethylbenzyl)-2,6-di-t-butylphenol,4-(α-methyl-4-methoxybenzyl)-2,6-di-t-butylphenol,4-methoxybenzyl-2,6-di-t-butylphenol,α-vinylbenzyl-3,4-methylenedioxy-6-alkoxybenzenes wherein the 6-alkoxygroup is allyloxy, methoxy, ethoxy, n-propoxy,6-(4-methoxybenzyl)-3,4-methylenedioxyphenol,α-methylbenzyl-3,4-methylenedioxy-6-methoxybenzene,α,α-dimethylbenzyl-3,4-methylenedioxy-6-alkoxybenzenes wherein the6-alkoxy group is methoxy, ethoxy, propoxy, butoxy, or pentoxy,α-methylbenzyl-3,4-methylenedioxy-6-alkoxybenzenes wherein the 6-alkoxygroup is methoxy or hexoxy,3-alkyl-4-hydroxybenzyl-3,4-methylenedioxybenzenes wherein the 3-alkylgroup is methyl or t-butyl,2-hydroxy-5-alkylbenzyl-3,4-methylenedioxybenzenes wherein the 5-alkylgroup is methyl or ethyl, 4-hydroxybenzyl-3,4-methylenedioxybenzene.

The compounds of the invention are especially effective asanti-procreants for flies or the order Diptera including, but notlimited to, the following families: Muscidae (housefly), Calliphoridae(screw-worm fly, blowfly, cluster fly), Tipulidae, Psychodidae,Culicidae, Blepharoceridae, Anisopidae, Cecidomyiidae, Bibionidae,Mycetophilidae, Simuliidae, Dixidae, Chironomidae, Mydaidae, Asilidae,Bombyliidae, Tabanidae, Stratiomyidae, Coenomyidae, Phoridae,Acroceridae, Nemestrinidae, Rhagionidae, Lonchopteridae, Dolichopodidae,Syrphidae, Asilidae, Scenopinidae, Apioceridae, Therevidae,Pipunculidae, Conopidae, Platypezidae, Empididae, Tachinidae,Sarcophagidae, Psilidae, Anthomyiidae, Gasterophilidae, Sepsidae,Helomyzidae, Tanypezidae, Canopidae, Ortalidae, Sciomyzidae,Sapromyzidae, Diposidae, Trypetidae, Borboridae, Ephydridae,Chloropodiae, Drosophilidae, Agromyzidae, Psilidae, Nycteribiidae,Streblidae, Hippoboscidae, and so forth.

EXAMPLES

The invention is further demonstrated by the following illustrativeexamples. Temperatures are in degrees Centigrade unless otherwiseindicated.

EXAMPLE 1 Synthesis of Group I Compounds

A. 4,6-Di-t-butyl-2-α-methylbenzylphenol: A solution of2,4-di-t-butylphenol (51 g) and 1-phenylethanol (31 g) in 40 ml ofacetic acid and 80 ml of formic acid was refluxed for 6 hours and thendiluted with 200 ml of water. The product was distilled giving 71.5 g ofa colorless oil, b.p. 157°-158° at 2 mm Hg. The molecular weight (mass )of the product as determined by mass spectrometry was 310.2308;calculated for C₂₂ H₃₀ O=310.2296. The proton magnetic resonance (pmr)spectrum of this compound at 100 MHz in deuterated chloroform (CDCl₃)exhibited absorbances as follows: δ1.34, 9 protons (H), singlet (S);δ1.55, 9H, S; δ1.65, 3H, doublet (D) (J=7.5 Hz); δ4.22, 1H, quartet (Q)(J=7.5 Hz); δ4.53, 1H, S; δ7.20, 7H, multiplet (M).

B. Similarly, 4,6-di-t-butyl-2-(α-methyl-4-methoxybenzyl)phenol wasprepared from 2,4-di-t-butylphenol and α-methyl-4-methoxybenzyl alcohol.A yellow oil (b.p. 180° at 1.0 mm Hg) which crystallized was obtained.The product was recrystallized from methanol to give colorless needlesmelting at room temperature (Found: C, 81.0; H, 9.45 Calc. for C₂₃ H₃₂O₂ : C, 81.1; H, 8.47%). The pmr spectrum determined as above exhibitedthe following: δ1.35, 9H, S; δ1.37, 9H, S; δ1.63, 3H, D (J=7 Hz); δ3.78,3H, S; δ4.17, Q, 1H (J=7 Hz); δ4.62, 1H, S; δ6.84, 2H, D (J=8 Hz);δ7.10-7.30, 4H, M.

C. 4,6-Di-t-butyl-2-(4-methoxybenzyl)phenol was prepared as follows: Asolution of 2,4-di-t-butylphenol (57.5 g), 4-methoxybenzyl alcohol (34.5g) and oxalic acid (2 g) in acetic acid (80 ml) and water (2 ml) wasrefluxed for 7 hours, diluted with water, and extracted with chloroform.Distillation of the chloroform extract gave an oil (b.p. 200°-210° C. at2 mm Hg) which crystallized (58 g; 71.4%). The product wasrecrystallized from methanol to give glistening colorless needles, m.p.84°-85° (Found: C, 81.0; H, 8.21. Calc. for C₂₂ H₃₀ O₂ : C, 80.9; H,9.26%). The pmr spectrum exhibited the following: δ1.30, 9H, S; δ1.38,9H, S; δ3.79, 3H, S; δ3.83, 2H, S; δ4.62, 1H, S; δ6.84, 2H, D (J=8 Hz);δ7.02, 1H, D (J=2 Hz); δ 7.14, 2H, D (J=8 Hz); δ7.23, 1H, D (J=Hz).

D. 2,4-Di-t-butyl-6-benzylphenol was prepared according to the methoddisclosed by H. A. Green, U.S. Pat. No. 3,193,526.

EXAMPLE 2 Synthesis of Group II Compounds

E. 2,6-Di-t-butyl-4-(α-methylbenzyl)phenol was prepared by refluxing2,6-di-t-butylphenol (51 g) and 1-phenylethanol (31 g) in acetic acid(40 ml) and formic acid (75 ml) as described for A. The product wasobtained as a colorless oil, b.p. 166°-168° at 1.0 mm Hg (62 g); (meas.mass=310.2309. Calc. for C₂₂ H₃₀ O=310.2296). The pmr spectrum was:δ1.40, 18H, S; δ1.61, 3H, D (J=8 Hz); δ4.06, 1H, Q (J=8 Hz); δ5.02, 1H,S; δ7.01, 2H, S; δ7.22, 5H, S.

F. 2,6-Di-t-butyl-4-(4-methoxybenzyl)phenol was prepared as describedfor A above. A mixture of 2,6-di-t-butylphenol (51.5 g), 4-methoxybenzylalcohol (34.5 g), formic acid (100 ml) and acetic acid (100 ml) wasrefluxed for 5 hours, diluted with water, and extracted with chloroform.Evaporation of the chloroform gave an oil which crystallized.Recrystallization from methanol gave colorless needles, mp 139° (58 g)(Found: C, 80.7; H, 9.30. Calc. for C₂₂ H₃₀ O₂ : C, 80.9; H, 9.26%); pmrspectrum: δ1.42, 18H, S; δ3.79, 3H, S; δ3.86, 2H, S; δ5.04, 1H, S;δ6.83, 2H, D (J=8 Hz); δ6.98, 2H, S; δ7.12, 2H, D (J=8 Hz).

G. 2,6-Di-t-butyl-4-(α-methyl-4-methoxybenzyl)phenol: Condensation of2,6-di-t-butylphenol (80 g) and α-methyl-4-methoxybenzyl alcohol (40 g)in acetic-formic acid solution as described for E above gave, ondistillation of the product, a colorless oil, b.p. 192°-201° at 2.0 mmHg (74 g). The oil crystallized from methanol to give glisteningcolorless needles, m.p. 83°-84° (49 g) (Found: C, 81.1; H, 9.42. Calc.for C₂₃ H₃₂ O₂ : C, 81.1; H, 9.47%); pmr spectrum: δ1.42, 18H, S; δ1.59,3H, D (J=7.5 Hz); δ3.77, 3H, S; δ4.03, 1H, Q (J=7.5 Hz); δ5.02, 1H, S;δ6.81, 2H, D (J=8.5 Hz); δ7.01, 2H, S; δ7.14, 2H, D (J=8.5 Hz).

EXAMPLE 3 Synthesis of Group III Compounds

H. (α-Methyl-4-methoxybenzyl)-3,4-methylenedioxy-6-methoxybenzene wasprepared according to the following procedure: A solution of sesamol(27.6 g, 0.2 mole), 1-(4-methoxyphenyl)ethanol (30.4 g, 0.2 mole), andoxalic acid (2 g) in glacial acetic acid (60 ml) and water (10 ml) wasrefluxed for 7 hours, diluted with water, and extracted with ether.Distillation of the ether extract gave an oil, b.p. 235°-237° at 5 mm Hg(53 g), which crystallized from benzene-skelly solve F to yieldglistening, colorless needles, m.p. 93°-94° (Found: C, 70.5; H, 5.86.Calc. for C₁₆ H₁₆ O₄ : C, 70.6; H, 5.92%); pmr spectrum: δ1.53, 3H, D(J=7 Hz); δ3.77, 3H, S; δ4.21, 1H, Q (J=7 Hz); δ4.58, 1H (OH), S; δ5.86,2H, S; δ6.35, 1H, S; δ6.70, 1H, S; δ6.81, 2H, D (J=9 Hz); δ7.17, 2H, D(J=9 Hz).

The above product was alkylated by refluxing its solution in acetone(13.6 g in 50 ml) with potassium carbonate (25 g) and excess (2 mol.equivs.) of methyl iodide for 20 hours. The reaction mixture was dilutedwith 5% aqueous sodium hydroxide (100 ml) and extracted with ether.Distillation gave a colorless oil, b.p. 184° at 1.0 mm Hg (Found: C,71.4; H, 6.41. Calc. for C₁₇ H₁₈ O₄ : C, 71.3; H, 6.34%); pmr spectrum:δ1.49, 3H, D (J=7 Hz); δ3.69, 3H, S; δ3.74, 3H, S; δ4.46, 1H, Q (J=7Hz); δ5.82, 2H, S; δ6.48, 1H, S; δ6.62, 1H, S; δ6.78, 2H, D (J=9 Hz);δ7.03, 2H, D (J=9 Hz).

I. (α-Methyl-4-methoxybenzyl)-3,4-methylenedioxy-6-n-propoxybenzene wasprepared by the procedure in H above and exhibited the followingproperties: colorless oil, b.p. 191°-192° at 1.0 mm Hg, which rapidlycrystallized (13.1 g). Recrystallization from methanol gave colorlessneedles, m.p. 84° (Found: C, 72.4; H, 7.09. Calc. for C₁₉ H₂₂ O₄ : C,72.6; H, 7.05%); pmr spectrum: δ0.97, 3H, triplet (T) (J=7 Hz); δ1.50,3H, D (J=7 Hz); δ1.70, 2H, M, (J=7 Hz); δ3.73, 3H, S; δ3.78, 2H, M;δ4.49, 1H, Q (J=7 Hz); δ5.81, 2H, S; δ6.46, 1H, S; δ6.64, 1H, S; δ6.78,2H, D (J=9 Hz); δ7.13, 2H, D (J=9 Hz).

J. Similarly (to H and I),(α-methyl-4-methoxybenzyl)-3,4-methylenedioxy-6-n-butoxybenzene wasprepared as a colorless oil, b.p. 202°-203° at 1.5 mm Hg (Found: C,73,4; H, 7.38. Calc. for C₂₀ H₂₄ O₄ : C, 73.1; H, 7.37%); pmr spectrum:δ0.93, 3H, T (J=7 Hz); δ1.48, 3h, D (J=8 Hz); δ1.55, 4H, M; δ3.76, 3H,S; δ3.80, Q (J=7 Hz); δ4.48, 1H, Q (J=8 Hz); δ5.83, 2H, S; δ6.47, 1H, S;δ6.63, 1H, S; δ6.78, 2H, D (J=9 Hz); δ7.12, 2H, D (J=9 Hz).

K. In the same way,(α-methyl-4-methoxybenzyl)-3,4-methylenedioxy-6-n-pentoxybenzene wasobtained as a yellow oil, b.p. 183°-200° C. at 5 mm Hg.

L. (4-Methoxybenzyl)-3,4-methylenedioxy-6-methoxybenzene was preparedfrom 6-(4-methoxybenzyl)-3,4-methylenedioxyphenol (L. Jurd, Tetrahedron,Vol. 33, pp. 163-168 (1977) by methylation as described above in H.Colorless prisms were obtained from benzene-solve F, m.p. 56°-57°(Found: C, 70.5; H, 5.95. Calc. for C₁₆ H₁₆ O₄ : C, 70.6; H, 5.92%); pmrspectrum: δ3.74, 3H, S; δ3.77, 3H, S; δ3.82, 2H, S; δ5.85, 2H, S; δ6.52,1H, S; δ6.55, 1H, S; δ6.80, 2H, D (J=9 Hz); δ7.11, 2H, D (J=9 Hz).

The following compounds (L through R) were prepared by the procedureused in K.

M. (4-Methoxybenzyl)-3,4-methylenedioxy-6-ethoxybenzene, slightly yellowoil, b.p. 178°-180° at 0.5 mm Hg (Found: C, 71.6; H, 6.38. Calc. for C₁₇H₁₈ O₄ : C, 71.3; H, 6.34%); pmr spectrum: δ1.34, 3H, T (J=7 Hz); δ3.76,3H, S; δ3.82, 2H, S; δ3.93, 2H, Q (J=7 Hz); δ5.84, 2H, S; δ6.49, 1H, S;δ6.56, 1H, S; δ6.79, 2H, D (J=9 Hz); δ7.10, 2H, D (J=9 Hz).

N. (4-Methoxybenzyl)-3,4-methylenedioxy-6n-propoxybenzene, colorlessoil, b.p. 183°-184° at 0.5 mm Hg (Found: C, 71.9; H, 6.64. Calc. for C₁₈H₂₀ O₄ : C, 72.0; H, 6.71%); pmr spectrum: δ1.00, 3H, T (J=7 Hz); δ1.76,2H, M; δ3.77, 3H, S; δ3.83, 4H, M; δ5.82, 2H, S; δ6.49, 1H, S; δ6.56,1H, S; δ6.78, 2H, D (J=9 Hz); δ7.01, 2H, D (J=9 Hz).

O. (4-Methoxybenzyl)-3,4-methylenedioxy-6-iso-propoxybenzene, colorlessoil, b.p. 176°-178° at 0.5 mm Hg (Found: C, 71.9; H, 6.64. Calc. for C₁₈H₂₀ O₄ : C, 72.0; H, 6.71%); pmr spectrum: δ1.24, 6H, D (J=6 Hz); δ3.76,3H, S; δ3.81, 2H, S; δ4.37, 1H, M (J=6 Hz); δ5.84, 2H, S; δ6.51, 1H, S;δ6.55, 1H, S; δ6.79, 2H, D (J=9 Hz); δ7.11, 2H, D (J=9 Hz).

P. (4-Methoxybenzyl)-3,4-methylenedioxy-6-n-butoxybenzene, colorlessoil, b.p. 192°-193° at 0.5 mm Hg (Found: C, 72.8; H, 7.09. Calc. for C₁₉H₂₂ O₄ : C, 72.6; H, 7.05%); pmr spectrum: δ0.94, 3H, T (J=7 Hz); δ1.54,4H, M; δ3.76, 3H, S; δ3.84, 4H, M; δ5.84, 2H, S; δ6.49, 1H, S; δ6.55,1H, S; δ6.78, 2H, D (J=9 Hz); δ7.10, 2H, D (J=9 Hz).

Q. (4-Methoxybenzyl)-3,4-methylenedioxy-6-iso-butoxybenzene, colorlessoil, b.p. 184°-186° at 0.5 mm Hg (Found: C, 72.5; H, 7.00. Calc. for C₁₉H₂₂ O₄ : C, 72.6; H, 7.05%); pmr spectrum: δ0.98, 6H, D (J=6 Hz); δ2.02,1H, M; δ3.74, 7H, M; δ5.81, 2H, S; δ6.48, 1H, S; δ6.56, 1H, S; δ6.78,2H, D (J=9 Hz); δ7.10, 2H, D (J=9 Hz).

R. (4-Methoxybenzyl)-3,4-ethylenedioxy-6-n-pentoxybenzene, colorlessoil, b.p. 194°-195° at 0.5 mm Hg (Found: C, 73.1; H, 7.42. Calc. for C₂₀H₂₄ O₄ : C, 73.1, H, 7.37%); pmr spectrum: δ0.90, 3H, T (J=6 Hz); δ1.36,4H, M; δ1.72, 2H, M; δ3.75, 3H, S; δ3.85, 4H, M; δ5.83, 2H, S; δ6.48,1H, S; δ6.55, 1H, S; δ6.78, 2H, D (J=9 Hz); δ7.10, 2H, D (J=9 Hz).

S. (4-Methoxybenzyl)-3,4-methylenedioxy-6-iso-pentoxybenzene, colorlessoil, b.p. 193° at 0.5 mm Hg (Found: C, 73.2; H, 7.40. Calc. for C₂₀ H₂₄O₄ : C, 73.1; H, 7.3%); pmr spectrum: δ0.92, 6H, D (J=6 Hz); δ1.68, 3H,M; δ3.76, 3H, S; δ3.84, 4H, M; δ5.82, 2H, S; δ6.49, 1H, S; δ6.56, 1H, S;δ6.78, 2H, D (J=9 Hz); δ7.08, 2H, D (J=9 Hz).

T. (α-Methylbenzyl)-3,4-methylenedioxy-6-methoxybenzene was prepared asfollows: A solution of sesamol (41.4 g), 1-phenylethyl alcohol (36.6 g)and oxalic acid (2 g) in acetic acid (100 ml) and water (10 ml) wasrefluxed for 24 hours and diluted with water. Distillation of the oilyproduct gave a pale yellow oil, b.p. 204°-205° at 4.0 mm Hg (56 g) whichcrystallized. Recrystallization from benzene-skelly solve F gave(α-methylbenzyl)-3,4-methylenedioxy-6-hydroxybenzene as colorlessneedles, m.p. 101°-102° (Found: C, 74.2, H, 5.75. Calc. for C₁₅ H₁₄ O₃ :C, 74.4; H, 5.83%); pmr spectrum: δ1.57, 3H, D (J=7 Hz); δ4.29, 1H, Q(J=7 Hz); δ4.50, 1H, S; δ5.86, 2H, S; δ6.35, 1H, S; δ6.72, 1H, S; δ7.25,5H, S.

The above product was methylated as described above in H yielding acolorless oil, b.p. 176° at 3.0 mm Hg (Found: C, 75.0; H, 6.37. Calc.for C₁₆ H₁₆ O₃ : C, 75.0; H, 6.29%); pmr spectrum: δ1.52, 3H, D (J=7Hz); δ3.66, 3H, S; δ4.52, 1H, Q (J=7 Hz); δ5.82, 2H, S; δ6.49, 1H, S;δ6.65, 1H, S; 7.22, 5H, S.

Similarly, compounds U through W were prepared.

U. (α-Methylbenzyl)-3,4-methylenedioxy-6-n-propoxybenzene, colorlessprisms from methanol, m.p. 63° (Found: C, 76.2; H, 7.15. Calc. for C₁₈H₂₀ O₃ : C, 76.0, H, 7.09%); pmr spectrum: δ0.96, 3H, T (J=7 Hz); δ1.52,3H, D (J=7 Hz); δ1.72, 2H, M (J=7 Hz); δ3.79, 2H, T (J=7 Hz); δ4.53, 1H,Q (J=7 Hz); δ5.81, 2H, S; δ6.46, 1H, S; δ6.67, 1H, S; δ7.20, 5H, S.

V. (α-Methylbenzyl)-3,4-methylenedioxy-6-n-butoxybenzene, colorlessneedles from methanol, m.p. 43° (Found: C, 76.3; H, 7.47. Calc. for C₁₉H₂₂ O₃ : C, 76.5; H, 7.43%); pmr spectrum: δ0.92, 3H, T (J=7 Hz); δ1.52,3H, D (J=7 Hz); δ1.55, 4H, M; δ3.82, 2H, T (J=7 Hz); δ4.52, 1H, Q (J=7Hz); δ5.84, 2H, S; δ6.48, 1h, S; δ6.67, 1H, S; δ7.21, 5H, M.

W. (α-Methylbenzyl)-3,4-methylenedioxy-6-n-pentoxybenzene, colorlessplates from methanol, m.p. 46°-47° (Found: C, 76.7; H, 7.80. Calc. forC₂₀ H₂₄ O₃ : C, 76.9; H, 7.74%); pmr spectrum: δ0.90, 3H, T (J=6 Hz);δ1.35, 4H, M; δ1.53, 3H, D (J=7 Hz); δ1.64, 2H, M; δ3.80, 2H, T (J=6Hz); δ4.51, 1H, Q (J=7 Hz); δ5.82, 2H, S; δ6.46, 1H, S; δ6.67, 2H, S;δ7.20, 5H, S.

X. (α,α-Dimethylbenzyl)-3,4-methylenedioxy-6-methoxybenzene was preparedas follows: A mixture of sesamol (44 g), α,α-dimethylbenzyl alcohol (44g), oxalic acid (3g), acetic acid (100 ml) and water (10 ml) wasrefluxed for 2.5 hours, diluted with water and extracted withchloroform. Distillation of the chloroform extract gave an oil, b.p.160°-163° at 0.5 mm Hg (60 g) which crystallized from aqueous methanolto give colorless needles, m.p. 75°-76° (Found: C, 75.0; H, 6.26. Calc.for C₁₆ H₁₆ O₃ : C, 75.0; H, 6.29%); pmr spectrum: δ1.63, 6H, S; 4.12,1H, S; δ5.81, 2H, S; δ6.33, 1H, S; δ6.98, 1H, S; δ6.31, 5H, S.

In a similar manner, the compounds Y-BB were prepared.

Y. (α,α-Dimethylbenzyl)-3,4-methylenedioxy-6-ethoxybenzene, colorlessneedles, m.p. 78°-79° (Found: C, 75.9; H, 7.15. Calc. for C₁₈ H₂₀ O₃ :C, 76.0, H, 7.09%); pmr spectrum: δ0.79, 3H, T (J=7 Hz); δ1.63, 6H, S;δ3.44, 2H, Q (J=7 Hz); δ5.90, 2H, S; δ6.42, 1H, S; δ7.02, 1H, S; δ7.17,5H, S.

Z. (α,α-Dimethylbenzyl)-3,4-methylenedioxy-6-n-propoxybenzene, colorlessplates, from methanol, m.p. 94° (Found: C, 76.4; H, 7.42. Calc. for C₁₉H₂₂ O₃ : C, 76.5; H, 7.43%); pmr spectrum: δ0.67, 3H, T (J=7 Hz); δ1.19,2H, M; δ1.64, 6H, S; δ3.37, 2H, T (J=7 Hz); δ5.91, 2H, S; δ6.43, 1H, S;δ7.23, 1H, S; δ7.36, 5H, S.

AA. (α, 60 -Dimethylbenzyl)-3,4-methylenedioxy-6-n-butoxybenzene,colorless plates from methanol, m.p. 89° (Found: C, 76.8, H, 7.67. Calc.for C₂₀ H₂₄ O₃ : C, 76.9; H, 7.74%); pmr spectrum: δ0.74, 3H, T (J=6Hz); δ1.10, 4H, M; δ1.62, 6H, S; δ3.39, 2H, T (J=6 Hz); δ5.88, 2H, S;δ6.41, 1H, S; δ7.02, 1H, S; δ7.15, 5H, S.

BB. (α,α-Dimethylbenzyl)-3,4-methylenedioxy-6-n-pentoxybenzene,colorless, flat needles from methanol, m.p. 55°-56° (Found: C, 77.3; H,8.01. Calc. for C₂₁ H₂₆ O₃ : C, 77.3; H, 7.66%); pmr spectrum: δ0.82,3H, T (J=7 Hz); δ1.32, 6H, M; δ1.62, 6H, S; δ3.42, 2H, T (J=7 Hz);δ5.91, 2H, S; δ6.42, 1H, S; δ7.03, 1H, S; δ7.16, 5H, S.

CC. (4-Methoxybenzyl)-3,4-methylenedioxy-6-(2-propenyl)benzene wasprepared according to the following procedure:

Safrole (34.4 g), 4-methoxybenzyl alcohol (34.4 g), and oxalic acid (3g) were refluxed in acetic acid (100 ml) and water (5 ml) for six hours.The oily product obtained on adding excess of water was extracted withether, dried, and distilled to give a colorless oil, b.p. 165°-167° at0.5 mm Hg (35 g) (Found: C, 76.8; H, 6.54, Calc. for C₁₈ H₁₈ O₃ : C,76.6; H, 6.43%); pmr spectrum: δ3.26, 2H, DT (J=7, 1.5 Hz); δ3.77, 3H,S; δ3.85, 2H, S; δ4.93, 1H, D of doublets (DD) (J=Q, 3, 1.5 Hz); δ5.07,DD (J=3, 1.5 Hz); δ5.81, 1H, M; δ5.88, 2H, S; δ6.58, 1H, S; δ6.67, 1H,S; δ6.80, 2H, D (J=9 Hz); δ7.02, 2H, D (J=9 Hz).

DD. (4-Methoxybenzyl)-3,4-methylenedioxy-6-n-propylbenzene was preparedby catalytic hydrogenation of CC in acetic acid in the presence ofpalladium charcoal. The product was a colorless oil, b.p. 169°-170° at0.5 mm Hg (Found: C, 76.4; H, 7.16. Calc. for C₁₈ H₂₀ O₃ : C, 76.0; H,7.09%); pmr spectrum: δ0.92, 3H, T (J=Hz); δ1.51, 2H, M (J=7 Hz); δ2.50,2H, T (J=7 Hz); δ3.77, 3H, S; δ3.86, 2H, S; δ5.86, 2H, S; δ6.55, 1H, S;δ6.67, 1H, S; δ6.80, 2H, D (J=9 Hz); δ7.02, 2H, D (J=9 Hz).

EE. (α-Vinylbenzyl)-3,4-methylenedioxy-6-methoxybenzene was obtained bymethylation of (α-vinylbenzyl)-3,4-methylenedioxy-6-hydroxybenzene(Jurd, Tetrahedron, Vol. 29, pp. 2347-2353, 1973) as described in Habove to give colorless needless from methanol, m.p. 92°-93° (Found: C,76.1; H, 6.01%).

The above procedure was employed to prepare FF and GG.

FF. (α-Vinylbenzyl)-3,4-methylenedioxy-6-ethoxybenzene, colorless grainsfrom methanol, m.p. 72°-73° (Found: C, 76.7, H, 6.45. Calc. for C₁₈ H₁₈O₃ : C, 76.6; H, 6.43%).

GG. (α-Vinylbenzyl)-3,4-methylenedioxy-6-n-propoxybenzene, colorlessthick needles from methanol, m.p. 92°-93° (Found: C, 76.3; H, 6.15.Calc. for C₁₇ H₁₆ O₃ : C, 76.1; H, 6.01%).

HH. (3-Methyl-4-methoxybenzyl)-3,4-methylenedioxybenzene was obtained asfollows: Ortho-cresol (40 g) was refluxed with piperonyl alcohol (30 g)in 80% formic acid (100 ml) for 1.5 hours and diluted with water.Distillation of the oily product gave a fraction, b.p. 178°-180° at 0.5mm Hg (34 g) which crystallized from benzene to give colorless needles,m.p. 95°; (Found: C, 74.3; H, 5.89. Calc. for C₁₅ H₁₄ O₃ : C, 74.4; H,5.83%); pmr spectrum: δ2.20, 3H, S; δ3.78, 2H, S; δ4.71, 1H, S; δ5.88,2H, S; δ6.76, 6H, M.

The so-prepared phenol was methylated as described above in H yieldingcolorless needles from skelly solve F, m.p. 34°-35° (Found: C, 75.3; H,6.43. Calc. for C₁₆ H₁₆ O₃ : C, 75.0; H, 6.29%); pmr spectrum: δ2.17,3H, S; δ3.74, 3H, S; δ3.76, 2H, S; δ5.80, 2H, S; δ6.86, 6H, M.

II. (3-Methyl-4-ethoxybenzyl)-3,4-methylenedioxybenzene was prepared asin HH. The product was a colorless oil, b.p. 165°-166° at 0.5 mm Hg; pmrspectrum: δ1.40, 3H, T (J=7 Hz); δ2.18, 3H, S; δ3.78, 2H, S; δ4.01, 2H,Q (J=7 Hz); δ5.88, 2H, S; δ6.80, 6H, M.

JJ. (3,5-Dimethyl-4-methoxybenzyl)-3,4-methylenedioxybenzene wasobtained as follows: 2,6-dimethylphenol (48.8 g), piperonyl alcohol(60.8 g) and oxalic acid (2 g) were refluxed in acetic acid (100 ml) andwater (10 ml) for 0.5 hours. Addition of water gave an oil which ondistillation gave a fraction, b.p. 206°-208° at 0.5 mm Hg (72 g). Thisoil crystallized from benzene-skelly solve F to give colorless needles,m.p. 85°; (Found: C, 75.2; H, 6.40. Calc. for C₁₆ H₁₆ O₃ : C, 75.0; H,6.29%); pmr spectrum: δ2.18, 6H, S; δ3.74, 2H, S; δ4.48, 1H, S; δ5,87,2H, S; δ6.69, 5H, M.

This phenolic product was methylated as in H above to give colorlessneedles from methanol, m.p. 44° (Found: C, 75.7; H, 6.68. Calc. for C₁₇H₁₈ O₃ : C, 75.5; H, 6.71%); pmr spectrum: δ2.24, 6H, S; δ3.69, 3H, S;δ3.76, 2H, S; δ5.88, 2H, S; δ6.63, 5H, M.

KK. Similarly, (3,5-dimethyl-4-methoxybenzyl)-3,4-methylenedioxybenzenewas obtained as methanol, m.p. 49° (Found: C, 76.0, H, 7.09. Calc. forC₁₈ H₂₀ O₃ : C, 76.0; H, 7.09%); pmr spectrum: δ1.39, 3H, T (J=7 Hz);δ2.23, 6H, S; δ3.81, 4H, M; δ5.88, 2H, S; δ6.73, 5H, M.

LL. (2,4-Dimethoxybenzyl)-3,4-methylenedioxybenzene was preparedaccording to the following procedure: A mixture of resorcinol (110 g)and piperonyl alcohol (76 g; 0.5 mol. equivalents) in 2% aqueous citricacid (1 liter) was refluxed for 15 hours and cooled. The crystallineproduct was recrystallized from benzene-skelly solve F to give colorlessneedles, m.p. 58°-59° (91 g) (Found: C, 68.8; H, 5.02. Calc. for C₁₄ H₁₂O₄ : C, 68.8; H, 4,95%); pmr spectrum: δ2.40, 1H, S (br); δ3.78, 2H, S;δ5.75, 1H, S (br); δ5.85, 2H, S; δ6.31, 2H, M; δ6.67, 3H, M; δ6.88, 1H,D (J=9 Hz).

The phenolic product was methylated as in H above to yield colorless,brittle prisms from skelly solve F, m.p. 51° (Found: C, 70.5; H, 5.90.Calc. for C₁₆ H₁₆ O₄ : C, 70.6; H, 5.92%); pmr spectrum: δ3.78, 8H, S;δ5.88, 2H, S; δ6.40, 2H, M; δ6.70, 3H, S; δ6.69, 1H, D (J=9 Hz).

EXAMPLE 4 Synthesis of Group IV Compounds

MM. (3,4-Methylenedioxy-6-methoxybenzyl)-3,4-methylenedioxybenzene wasprepared as follows: A solution of sesamol (13.4 g) and piperonylalcohol (15.2 g) in 2% aqueous citric acid (250 ml) was refluxed for 2hours and cooled. The oily product crystallized and was recrystallizedfrom methanol to give colorless plates, m.p. 143° (Found: C, 66.2; H,4.42. Calc. for C₁₅ H₁₂ O₅ : C, 66.2; H, 4.44%); pmr spectrum: δ3.79,2H, δ4.55, 1H, S; δ5.87, 2H, S; δ5.90, 2H, S; δ6.38, 1H, S; δ6.57, 1H,S; δ6.70, 3H, M.

Methylation of the so-produced phenol as in H above gave colorlessneedles from acetone-methanol, m.p. 106°-107° (Found: C, 67.0; H, 4.89.Calc. for C₁₆ H₁₄ O₅ : C, 67.1; H, 4.93%); pmr spectrum: δ3.75, 3H, S;δ3.79, 2H, S; δ5.88, 2H, S; δ5.89, 2H, S; δ6.56, 1H, S; δ6.52, 1H, S;δ6.67, 3H, S.

NN. Similarly,(3,4-methylenedioxy-6-ethoxybenzyl)-3,4-methylenedioxybenzene wasobtained as colorless needles from methanol, m.p. 44° (Found: C, 68.1;H, 5.29. Calc. for C₁₇ H₁₆ O₅ : C, 68.0; H, 5.37%); pmr spectrum: δ1.36,3H, T (J=7 Hz); δ3.79, 3H, S; δ3.92, 2H, Q (J=7 Hz); δ5.84, 2H, S;δ3.87, 2H, S; δ6.50, 1H, S; δ6.58, 1H, S; δ6.70, 3H, S.

EXAMPLE 5 Novel Synthesis of Group I Compounds

4,6-Di-t-butyl-2-(4-methoxybenzyl)phenol (C above) was prepared byheating a mixture of 2,4-di-t-butylphenol (41.2 g),4-methoxybenzylalcohol (27.6 g) and toluene (5.0 ml) at 210°-220° C. ina flask fitted with a Dean-Stark trap filled with toluene. After 2 hoursthe reaction mixture was distilled under reduced pressure to give a paleyellow oil (57.6 g) which subsequently crystallized. The physicalproperties of the crystalline product were identical to that for theproduct in C above.

EXAMPLE 6 Anti-Procreant Tests with Group I Compounds

The compound to be tested was administered in a standard fly foodcontaining 6 parts of sugar, 6 parts of powdered non-fat dry milk, and 1part of powdered egg yolk. Treated food was prepared by mixing anappropriate amount of a solution or suspension of CBCP in acetone with abatch of the food. The acetone was evaporated (4-6 hours) and the drymaterial was repulverized.

Oviposition inhibition tests: Samples of treated food with a containerof water were placed in cages containing 100 newly-emerged adult flies(family Muscidae). After the flies had been exposed to the treated dietfor 6-7 days, 1/2 inch of moist standard fly larva-rearing medium (CSMA)in souffle cups was placed in the cages for oviposition. After 4-6hours, the cup was removed and examined for eggs. If no eggs were laid,the medium was offered again at intervals of 1 or 2 days until it hadbeen offered three times or the flies had oviposited.

Chemosterilancy tests: If eggs were laid in the above tests, the cupswere filled with water and stirred to break up the egg masses. A randomsample of 100 eggs from each cup was collected and placed on a smallpiece of black cloth which was then laid on top of moist larva-rearingmedium in a rearing container. Observations were made to determinepercentage of egg hatch and pupal development.

In those cases where the preliminary tests indicated that sterility hadoccurred in the flies fed the treated food, 10 males were removed fromthe test cage and crossed with 10 virgin, 4-day old, untreated females.These flies were maintained on untreated fly food. After 5 days, cupscontaining the larval-rearing medium was provided as previouslydescribed and a 100-egg sample was collected and place on moistlarve-rearing medium. About a week after oviposition, examination wasmade to determine the percentage of hatched eggs and of pupae developed.

The results of the oviposition inhibition tests and the chemosterilancytests are summarized below:

    ______________________________________                     Mortality,             Pupal            Amount   parent           Egg   develop-    Compound            in food  generation                               Ovi-   hatch ment    used    (%)      (%)       position                                      (%)   (%)    ______________________________________    C       1.0      0         None   --    --            0.5      0         None   --    --            0.25*    0         Normal 0     0            0.1      0         "      0     0            0.05     0         "      0     0            0.025    0         "      0     0            0.01     0         "      45    45    A       0.25     0         "      0     0            0.1      0         "      0     0            0.05     0         "      0     0            0.025    0         "      28    28            0.01     0         "      39    39    B       1.0      0         "      0     0            0.5      0         "      0     0            0.25     0         "      18    18    D       1.0*     0         "      0     0            0.5      0         "      0     0            0.25     0         "      0     0            0.1      0         "      0     0            0.05     0         "      90    90    None    0        0         Normal 92-93 92-93    ______________________________________     *100% sterilization of males at this concentration.

For purpose of comparison the above-described tests were applied to2-benzyl-4-t-butylphenol and 2-(α-methylbenzyl)-4-t-butylphenol. Thetests demonstrated that these compounds were ineffective in inducingsexual sterility or in inhibiting oviposition.

EXAMPLE 7 Anti-Procreant Tests with Group II Compound

The procedure outlined in Example 6 was followed using a Group IIcompound. The results are tabularized below.

    ______________________________________                     Mortality,             Pupal            Amount   parent           Egg   develop-    Compound            in food  generation                               Ovi-   hatch ment    used    (%)      (%)       position                                      (%)   (%)    ______________________________________    E       1.0      0         Normal 0     0            0.5      0         "      0     0            0.25     0         "      0     0            0.1      0         "      36    36    None    0        0         Normal 92-93 92-93    ______________________________________

For purposes of comparison the above-described tests were applied to2,6-di-t-butyl-4-(4-methoxybenzyl) phenol and2,6-di-t-butyl-4-(α-methyl-4-methoxybenzyl)phenol, both compounds beingineffective in inducing sexual sterility or in inhibiting oviposition.

EXAMPLE 8 Anti-Procreant Tests with Group III Compounds

The procedure outlined in Example 6 was followed using Group IIIcompounds. The results are summarized below:

    ______________________________________                     Mortality,             Pupal            Amount   parent           Egg   develop-    Compound            in food  generation                               Ovi-   hatch ment    used    (%)      (%)       position                                      (%)   (%)    ______________________________________    H       0.025    0         Normal 45    45            0.01     0         "      14    14    I       1.0*     0         None   --    --            0.025    0         Normal 38    38            0.01     0         "      63    63    J       0.01     0         "      2     2            0.05     0         "      3     3            0.025    0         "      61    61            0.01     0         "      30    30    K       1.0      0         "      0     0            0.5      0         "      0     0            0.25     0         "      0     0            0.1      0         "      70    70    L       0.25     60        None   --    --            0.1      0         Normal 0     0            0.05     0         "      0     0            0.01     0         "      91    91    M       0.1      0         None   --    --            0.05     0         Normal 0     0            0.025    0         "      0     0            0.01     0         "      19    19    N       0.25     75        None   --    --            0.1      0         Normal 0     0            0.05     0         "      33    33    O       0.5      80        None   --    --            0.25     0         Normal 0     0            0.05     0         "      48    48    P       0.5      0         Normal 0     0            0.25     0         "      0     0            0.1      0         "      10    10            0.05     0         "      36    36    Q       0.5      90        None   --    --            0.25     0         Normal 0     0            0.1      0         "      0     0            0.05     0         "      28    28    R       0.25     0         "      0     0            0.1      0         "      31    31            0.05     0         "      76    76    S       0.5      0         "      0     0            0.25     0         "      0     0            0.1      0         "      6     6            0.05     0         "      55    55    T       0.5      42        "      0     0            0.25     60        "      56    56    U       1.0      0         "      0     0            0.5      0         "      0     0            0.25     0         "      0     0            0.1      0         "      0     0            0.05     0         "      0     0            0.025    0         "      42    42    V       0.5      0         "      34    34    CC      0.25     50        None   --    --            0.1      0         "      --    --            0.05     0         "      --    --            0.025    0         Normal 0     0            0.01     0         "      15    15    DD      0.25     0         None   --    --            0.1      0         Normal 0     0            0.05     0         "      0     0            0.025    0         "      7     7    HH      0.25     80        None   --    --            0.1      0         Normal 82    82    II      0.5      80        None   --    --            0.25     0         Normal 50    50    JJ      0.5      70        None   --    --            0.25     0         Normal 0     0            0.1      0         "      6     6            0.05     0         "      70    70    KK      0.5      85        None   --    --            0.25     0         Normal 85    85    LL      0.25     60        None   --    --            0.1      0         Normal 76    76    None    0        0         "      92-93 92-93    ______________________________________     *100% sterilization of males at this concentration.

For purposes of comparison the following compounds were tested and foundto be ineffective in inducing sexual sterility or in inhibitingoviposition: 2-(4-methoxybenzyl)-3,4-methylenedioxyphenol,(α-methylbenzyl)-3,4-methylenedioxy-6-methoxybenzene,(α,α-dimethylbenzyl)-3,4-methylenedioxy-6-methoxybenzene,(α,α-dimethylbenzyl)-3,4-methylenedioxy-6-ethoxybenzene,(α,α-dimethylbenzyl)-3,4-methylenedioxy-6-n-propoxybenzene,(α,α-dimethylbenzyl)-3,4-methylenedioxy-6-n-butoxybenzene,(α,α-dimethylbenzyl)-3,4-methylenedioxy-6-n-pentoxybenzene,(α-vinylbenzyl)-3,4-methylenedioxy-6-methoxybenzene,(α-vinylbenzyl)-3,4-methylenedioxy-6-ethoxybenzene,(α-vinylbenzyl)-3,4-methylenedioxy-6-n-propoxybenzene.

EXAMPLE 9 Anti-Procreant Tests with Group IV Compound

The procedure outlined in Example 6 was followed substituting a Group IVcompound for those of Group I. The table below provides a summary ofresults.

    ______________________________________                     Mortality,             Pupal            Amount   parent           Egg   develop-    Compound            in food  generation                               Ovi-   hatch ment    used    (%)      (%)       position                                      (%)   (%)    ______________________________________    NN      0.1      0         Normal 0     0            0.05     0         "      2     2    None    0        0         "      92-93 92-93    ______________________________________

(3,4-Methylenedioxy-6-methoxybenzyl)-3,4-methylenedioxybenzene wastested for purposes of comparison and was found to be ineffective ininducing sexual sterility or in inhibiting oviposition.

EXAMPLE 10 Growth-Inhibition Tests

The compound to be tested was added to one liter of water until thefinal concentration thereof was a growth-inhibiting amount. Fifty earlyfourth-stage larvae of the common malaria mosquito (Anophelesquadrimaculatus) were placed on this water. Larval food was administereddaily. Dead larvae and pupae were removed, counted, and discarded daily.Live pupae were removed, rinsed, and transferred to a cup of distilledwater. The cup was placed in an emergence cage, and the emerging adults,if any, were maintained on a sugar-water diet.

Two days after the last pupation, the pupal cups were observed for thenumber of dead pupae and the number of adults that were dead, unable tocomplete eclosion, or malformed. The effectiveness of the compound ininhibiting growth was determined by adding the number of dead larvae andpupae and the number of adults that were dead, unable to completeeclosion, and malformed. This sum was corrected by Abbott's formula (toadjust for the number of larvae or pupae which would die naturally) anddesignated as the GI (growth inhibition). The results are expressed asGI-90, i.e., the concentration of growth inhibitor in ppm that wouldprevent and/or retard growth in 90% of the treated larvae.

The results are summarized in the following table.

    ______________________________________    Compound      GI-90 (ppm)    ______________________________________    F             0.042    P             0.047    S             0.036    Q             0.082    A             0.039    K             0.060    I             0.042    J             0.025    V             0.097    E             0.072    JJ            0.6    KK            0.9    LL            0.2    O             0.8    CC            0.2    DD            0.2    T             0.6    W             0.2    H             0.5    U             0.3    ______________________________________

EXAMPLE 11 Anti-Procreant Tests on Screw-worm Fly

These tests were conducted on mass-reared screwworm flies which had beenobtained as pupae from the screwworm fly plant at Mission, Texas. Theflies were held in cages with water and undiluted corn syrup in a colonyroom maintained at about 27° C. and 60% relative humidity (RH) with a12-hour photoperiod beginning at 6 a.m. Adults that emerged were lightlyanesthetized with CO₂ for ease of manipulation the same day.

The compounds tested (D, C, A, M, CC) all had low solubility in water,so the flies were offered the chemosterilants in a corn syrup mixture,the compounds being homogenized in the syrup by gradual mixing in apestle and mortar. The mixtures obtained were fed to the flies in"Dixie" paper cups, 7 cm diameter, and rice hulls were placed on thesurface of the food to prevent the flies from getting stuck in theviscous mixture.

Initially, varying concentrations of a chemosterilant were fed to theflies for the first 5 days of life. Thereafter, the chemosterilant wasreplaced with pure corn syrup. On the 7th day, 3 replicates of 10 flieswere stimulated to oviposit and the flies which oviposited were checkedfor insemination by an examination of the spermathecae for live sperms.The total number of eggs per fly was estimated and the hatchability ofthese eggs (fertility) was determined 24 hours later (at 37° C.).Observations were made to determine percentage of egg hatch.

The results are summarized in the following table.

    ______________________________________    Amount       Survival   Ovi-     Inhibition of    Compound            in       Male   Female                                  position                                         embryogenesis    used    food (%) (%)    (%)   (%)    (%)    ______________________________________    None             50.0   81.3  83.3   --    A       0.01     54.0   71.3  63.3   100            0.10     47.0   68.0  90.0   100    D       0.01     46.0   49.3  66.7   95.2            0.10     55.0   88.7  95.0   100    CC      0.10     45.0   92.7  65.0   100    M       0.10     35.0   88.7  55.0   99.8    C       0.10     63.0   66.0  75.0   100    ______________________________________

EXAMPLE 12 Mutagenicity and Toxicity Studies

The mutagenic activity of D, A, B, M, N, and CC were tested by thestandard Ames' Salmonella/microsome procedure, which is reported to showbetter than 90% correlation with development of mammalian cancers (Ameset al., Mutation Research, Vol. 31, p. 347, 1975; McCann et al., Proc.Nat. Acad. Sci., Vol. 72, p. 5135, 1975). Tester strains TA-100, TA-98,TA-1537 and the plate test method were used, employing concentrations of10, 100, 1000, and 10,000 of compound per plate. The metabolicactivation mixture (S-9 mix) used the 9000 times g supernatant ofArochlor-1254-induced rat liver homogenate at a level of 100 μl per mlof S-9 mix. The results indicate that in the strains tested compounds A,B, N, and CC are non-mutagenic, either without or with metabolicactivation. Compounds D and M did exhibit revertant frequencies whichexceeded the mean control value plus two or three standard deviations atdoses between 10-10,000 μg/plate in TA-100 and S-9. This response isextremely weak relative to known mutagenic agents which revert thisstrain.

Compounds D, A, and B were also assayed for oral toxicity in mice.Estimated LD₅₀ for D, A, and B were 3430, 2510 and 3550 mg/kg bodyweight, respectively, indicating that these compounds are only slightlytoxic.

Having thus described my invention, I claim:
 1. A method of inhibitingprocreation in insects, which comprisesadministering to the insects acompound selected from the group consisting of (a) compounds of thestructure ##STR17## wherein n is an integer from 1 to 3, R is hydrogenor lower alkyl containing from 1 to 6 carbon atoms, and R₁ is hydrogen,lower alkyl containing from 1 to 6 carbon atoms or lower alkoxycontaining from 1 to 6 carbon atoms, (b) compounds of the structure##STR18## wherein R₂ is hydrogen, lower alkyl containing from 1 to 6carbon atoms, lower alkoxy containing from 1 to 6 carbon atoms, or loweralkenyl containing from 2 to 6 carbon atoms, R₃ is hydrogen or loweralkyl containing from 1 to 6 carbon atoms, R₄, R₅, and R₆ areindependently hydrogen, lower alkyl containing from 1 to 6 carbon atoms,and lower alkoxy containing from 1 to 6 carbon atoms, and wherein, if R₂is hydrogen, then R₅ and R₆ must be independently lower alkyl containingfrom 1 to 6 carbon atoms or lower alkoxy containing from 1 to 6 carbonatoms, and wherein, if R₄, R₅, and R₆ are hydrogen and R₃ is methyl thenR₂ must be lower alkoxy containing from 2 to 5 carbon atoms, (c)compounds of the structure ##STR19## wherein R₇ is lower alkylcontaining from 1 to 6 carbon atoms or lower alkoxy containing from 2 to6 carbon atoms or lower alkenyl containing from 2 to 6 carbon atoms andR₈ is hydrogen or lower alkyl containing from 1 to 6 carbon atoms, and(d) compounds of the structure ##STR20## wherein R is hydrogen or loweralkyl containing from 1 to 6 carbon atoms, said compound beingadministered in an amount insufficient to kill the insects butsufficient to inhibit procreation therein.
 2. The method of claim 1wherein the compound inhibits oviposition in insects thereby inhibitingprocreation and the compound is administered in an amount sufficient toinhibit oviposition.
 3. The method of claim 1 wherein the compoundcauses sexual sterility in insects thereby inhibiting procreation andthe compound is administered in an amount sufficient to cause sexualsterility.
 4. The method of claim 1 wherein the compound is2,4-di-t-butyl-6-(4-methoxybenzyl) phenol.
 5. The method of claim 1wherein the compound is 2,4-di-t-butyl-6-(α-methylbenzyl) phenol.
 6. Themethod of claim 1 wherein the compound is a(4-methoxybenzyl)-3,4-methylenedioxy-6-alkoxybenzene wherein the alkoxygroup is methoxy, ethoxy, propoxy, butoxy, pentoxy, or hexoxy.
 7. Themethod of claim 1 wherein the compound is an(α-methyl-4-methoxybenzyl)-3,4-methylenedioxy-6-alkoxybenzene whereinthe alkoxy group is methoxy, ethoxy, propoxy, butoxy, pentoxy, orhexoxy.
 8. The method of claim 1 wherein the compound is an(α-methylbenzyl)-3,4-methylenedioxy-6-alkoxybenzene wherein the alkoxygroup is ethoxy, propoxy, butoxy, or pentoxy.
 9. The method of claim 1wherein the compound is a(4-methoxybenzyl)-3,4-methylenedioxy-6-alkenylbenzene wherein thealkenyl group is ethenyl, propenyl, butenyl, pentenyl, or hexenyl. 10.The method of claim 1 wherein the compound is a(4-methoxybenzyl)-3,4-methylenedioxy-6-alkylbenzene wherein the alkylgroup is methyl, ethyl, propyl, butyl, pentyl, or hexyl.
 11. The methodof claim 1 wherein the compound is(3,4-methylenedioxy-6-ethoxybenzyl)-3,4-methylenedioxybenzene.